tbuckley/cabot-search huggingface dataset:
Kate Schroder: Gender equality in STEM
Authors: Lucie Van Emmenis
Journal: The Journal of Experimental Medicine (2023)

Kate Schroder is a professor and director of the Centre for Inflammation and Disease Research at the Institute for Molecular Bioscience (IMB), University of Queensland, Australia. Her lab, the IMB Inflammasome Laboratory, is interested in the mechanisms that underlie inflammasome activity and inhibition, regulators of inflammasome-dependent inflammation, and caspase activation. We recently got the opportunity to speak with Kate about gender equality in science, technology, engineering, and mathematics (STEM). We covered steps her institute is taking to improve gender equality in the workplace, advice for female early career researchers (ECRs), and how something as simple as a robot vacuum cleaner can make a huge difference to a person's life.
Arthropod-borne diseases among travellers arriving in Europe from Africa, 2015 to 2019
Authors: Céline M Gossner, Luisa Hallmaier-Wacker, Olivier Briet, Joana M Haussig, Henriette de Valk, Ariana Wijermans, Tamas Bakonyi, Theresa Madubuko, Christina Frank, Harold Noel, Mohammed Abdulaziz
Journal: Eurosurveillance (2023)

BackgroundTravellers are generally considered good sentinels for infectious disease surveillance.AimTo investigate whether health data from travellers arriving from Africa to Europe could provide evidence to support surveillance systems in Africa.MethodsWe examined disease occurrence and estimated risk of infection among travellers arriving from Africa to Europe from 2015 to 2019 using surveillance data of arthropod-borne disease cases collected through The European Surveillance System (TESSy) and flight passenger volumes from the International Air Transport Association.ResultsMalaria was the most common arthropod-borne disease reported among travellers from Africa, with 34,235 cases. The malaria travellers' infection rate (TIR) was 28.8 cases per 100,000 travellers, which is 36 and 144 times higher than the TIR for dengue and chikungunya, respectively. The malaria TIR was highest among travellers arriving from Central and Western Africa. There were 956 and 161 diagnosed imported cases of dengue and chikungunya, respectively. The highest TIR was among travellers arriving from Central, Eastern and Western Africa for dengue and from Central Africa for chikungunya in this period. Limited numbers of cases of Zika virus disease, West Nile virus infection, Rift Valley fever and yellow fever were reported.ConclusionsDespite some limitations, travellers' health data can efficiently complement local surveillance data in Africa, particularly when the country or region has a sub-optimal surveillance system. The sharing of anonymised traveller health data between regions/continents should be encouraged.
Impaired protein hydroxylase activity causes replication stress and developmental abnormalities in humans
Authors: Sally C. Fletcher, Charlotte Hall, Tristan J. Kennedy, Sander Pajusalu, Monica H. Wojcik, Uncaar Boora, Chan Li, Kaisa Teele Oja, Eline Hendrix, Christian A.E. Westrip, Regina Andrijes, Sonia K. Piasecka, Mansi Singh, Mohammed E. El-Asrag, Anetta Ptasinska, Vallo Tillmann, Martin R. Higgs, Deanna A. Carere, Andrew D. Beggs, John Pappas, Rachel Rabin, Stephen J. Smerdon, Grant S. Stewart, Katrin Õunap, Mathew L. Coleman
Journal: Journal of Clinical Investigation (2023)

Although protein hydroxylation is a relatively poorly characterized posttranslational modification, it has received significant recent attention following seminal work uncovering its role in oxygen sensing and hypoxia biology. Although the fundamental importance of protein hydroxylases in biology is becoming clear, the biochemical targets and cellular functions often remain enigmatic. JMJD5 is a "JmjC-only" protein hydroxylase that is essential for murine embryonic development and viability. However, no germline variants in JmjC-only hydroxylases, including JMJD5, have yet been described that are associated with any human pathology. Here we demonstrate that biallelic germline JMJD5 pathogenic variants are deleterious to JMJD5 mRNA splicing, protein stability, and hydroxylase activity, resulting in a human developmental disorder characterized by severe failure to thrive, intellectual disability, and facial dysmorphism. We show that the underlying cellular phenotype is associated with increased DNA replication stress and that this is critically dependent on the protein hydroxylase activity of JMJD5. This work contributes to our growing understanding of the role and importance of protein hydroxylases in human development and disease.
Protease allergens as initiators–regulators of allergic inflammation
Authors: Wai Tuck Soh, Jihui Zhang, Morley D. Hollenberg, Harissios Vliagoftis, Marc E. Rothenberg, Caroline L. Sokol, Clive Robinson, Alain Jacquet
Journal: Allergy (2023)

Abstract Tremendous progress in the last few years has been made to explain how seemingly harmless environmental proteins from different origins can induce potent Th2‐biased inflammatory responses. Convergent findings have shown the key roles of allergens displaying proteolytic activity in the initiation and progression of the allergic response. Through their propensity to activate IgE‐independent inflammatory pathways, certain allergenic proteases are now considered as initiators for sensitization to themselves and to non‐protease allergens. The protease allergens degrade junctional proteins of keratinocytes or airway epithelium to facilitate allergen delivery across the epithelial barrier and their subsequent uptake by antigen‐presenting cells. Epithelial injuries mediated by these proteases together with their sensing by protease‐activated receptors (PARs) elicit potent inflammatory responses resulting in the release of pro‐Th2 cytokines (IL‐6, IL‐25, IL‐1β, TSLP) and danger‐associated molecular patterns (DAMPs; IL‐33, ATP, uric acid). Recently, protease allergens were shown to cleave the protease sensor domain of IL‐33 to produce a super‐active form of the alarmin. At the same time, proteolytic cleavage of fibrinogen can trigger TLR4 signaling, and cleavage of various cell surface receptors further shape the Th2 polarization. Remarkably, the sensing of protease allergens by nociceptive neurons can represent a primary step in the development of the allergic response. The goal of this review is to highlight the multiple innate immune mechanisms triggered by protease allergens that converge to initiate the allergic response.
Higher risk of SARS-CoV-2 Omicron BA.4/5 infection than of BA.2 infection after previous BA.1 infection, the Netherlands, 2 May to 24 July 2022
Authors: Stijn P Andeweg, Brechje de Gier, Harry Vennema, Ivo van Walle, Noortje van Maarseveen, Nina E Kusters, Hester E de Melker, Susan JM Hahné, Susan van den Hof, Dirk Eggink, Mirjam J Knol
Journal: Eurosurveillance (2023)

BackgroundIn summer 2022, SARS-CoV-2 Omicron BA.5 became dominant in Europe. In vitro studies have shown a large reduction of antibody neutralisation for this variant.AimWe aimed to investigate differences in protection from previous infection and/or vaccination against infection with Omicron BA.4/5 vs BA.2.MethodsWe employed a case-only approach including positive PCR tests from community testing between 2 May and 24 July 2022 that were tested for S gene target failure (SGTF), which distinguishes BA.4/5 from BA.2 infection. Previous infections were categorised by variant using whole genome sequencing or SGTF. We estimated by logistic regression the association of SGTF with vaccination and/or previous infection, and of SGTF of the current infection with the variant of the previous infection, adjusting for testing week, age group and sex.ResultsThe percentage of registered previous SARS-CoV-2 infections was higher among 19,836 persons infected with Omicron BA.4/5 than among 7,052 persons infected with BA.2 (31.3% vs 20.0%). Adjusting for testing week, age group and sex, the adjusted odds ratio (aOR) was 1.4 (95% CI: 1.3-1.5). The distribution of vaccination status did not differ for BA.4/5 vs BA.2 infections (aOR = 1.1 for primary and booster vaccination). Among persons with a previous infection, those currently infected with BA4/5 had a shorter interval between infections, and the previous infection was more often caused by BA.1, compared with those currently infected with BA.2 (aOR = 1.9; 95% CI: 1.5-2.6).ConclusionOur results suggest immunity induced by BA.1 is less effective against BA.4/5 infection than against BA.2 infection.
Diagnostic, Prognostic, and Predictive Role of Ki67 Proliferative Index in Neuroendocrine and Endocrine Neoplasms: Past, Present, and Future
Authors: Stefano La Rosa
Journal: Endocrine Pathology (2023)

Abstract The introduction of Ki67 immunohistochemistry in the work-up of neuroendocrine neoplasms (NENs) has opened a new approach for their diagnosis and prognostic evaluation. Since the first demonstration of the prognostic role of Ki67 proliferative index in pancreatic NENs in 1996, several studies have been performed to explore its prognostic, diagnostic, and predictive role in other neuroendocrine and endocrine neoplasms. A large amount of information is now available and published results globally indicate that Ki67 proliferative index is useful to this scope, although some differences exist in relation to tumor site and type. In gut and pancreatic NENs, the Ki67 proliferative index has a well-documented and accepted diagnostic and prognostic role and its evaluation is mandatory in their diagnostic work-up. In the lung, the Ki67 index is recommended for the diagnosis of NENs on biopsy specimens, but its diagnostic role in surgical specimens still remains to be officially accepted, although its prognostic role is now well documented. In other organs, such as the pituitary, parathyroid, thyroid (follicular cell-derived neoplasms), and adrenal medulla, the Ki67 index does not play a diagnostic role and its prognostic value still remains a controversial issue. In medullary thyroid carcinoma, the Ki67 labelling index is used to define the tumor grade together with other morphological parameters, while in the adrenal cortical carcinoma, it is useful to select patients to treated with mitotane therapy. In the present review, the most important information on the diagnostic, prognostic, and predictive role of Ki67 proliferative index is presented discussing the current knowledge. In addition, technical issues related to the evaluation of Ki67 proliferative index and the future perspectives of the application of Ki67 immunostaining in endocrine and neuroendocrine neoplasms is discussed.
KDM6B protects T-ALL cells from NOTCH1-induced oncogenic stress
Authors: Nancy Issa, Hassan Bjeije, Elisabeth R. Wilson, Aishwarya Krishnan, Wangisa M. B. Dunuwille, Tyler M. Parsons, Christine R. Zhang, Wentao Han, Andrew L. Young, Zhizhong Ren, Kai Ge, Eunice S. Wang, Andrew P. Weng, Amanda Cashen, David H. Spencer, Grant A. Challen
Journal: Leukemia (2023)
Exploiting PRMT5 as a target for combination therapy in mantle cell lymphoma characterized by frequent ATM and TP53 mutations
Authors: Yuxuan Che, Yang Liu, Yixin Yao, Holly A. Hill, Yijing Li, Qingsong Cai, Fangfang Yan, Preetesh Jain, Wei Wang, Lixin Rui, Michael Wang
Journal: Blood Cancer Journal (2023)

Constant challenges for the treatment of mantle cell lymphoma (MCL) remain to be recurrent relapses and therapy resistance, especially in patients harboring somatic mutations in the tumor suppressors ATM and TP53, which are accumulated as therapy resistance emerges and the disease progresses, consistent with our OncoPrint results that ATM and TP53 alterations were most frequent in relapsed/refractory (R/R) MCL. We demonstrated that protein arginine methyltransferase-5 (PRMT5) was upregulated in R/R MCL, which predicted a poor prognosis. PRMT5 inhibitors displayed profound antitumor effects in the mouse models of MCL with mutated ATM and/or TP53, or refractory to CD19-targeted CAR T-cell therapy. Genetic knockout of PRMT5 robustly inhibited tumor growth in vivo. Co-targeting PRMT5, and ATR or CDK4 by using their inhibitors showed synergistic antitumor effects both in vitro and in vivo. Our results have provided a rational combination therapeutic strategy targeting multiple PRMT5-coordinated tumor-promoting processes for the treatment of R/R MCL with high mutation burdens.
CPX-351 (Vyxeos™) treatment in blast-phase myeloproliferative neoplasm (MPN-BP): real-world experience in 12 consecutive cases
Authors: Rimal Ilyas, Kristen McCullough, Talha Badar, Mrinal M. Patnaik, Hassan Alkhateeb, Abhishek Mangaonkar, Animesh Pardanani, Ayalew Tefferi, Naseema Gangat
Journal: Blood Cancer Journal (2023)
A novel salvage method to recapture the maldeployed distal flange of a lumen-apposing metal stent
Authors: Roderick Prawiradiradja, Michael Ding, Chia Chuin Yau, Wai Liam Lam, Damien Durkin, Srisha Hebbar
Journal: Endoscopy (2023)

Endoscopic ultrasonography-guided choledochoduodenostomy (EUS-CDS) using an electrocautery-enhanced lumen-apposing metal stent (LAMS) is an effective tool in the endoscopic management of biliary obstruction [1]. Complications can occur during delivery of the LAMS, and these include maldeployment [2]. Several salvage methods have been described, such as stent-in stent, position adjustment post-full deployment [3], and natural orifice transluminal endoscopic surgery (NOTES) [4]. We describe a novel salvage method to recapture a partially deployed LAMS ([Video 1]).
Clip and dental floss traction-assisted endoscopic mucosal resection for early carcinoma of the duodenal papilla
Authors: Dazhou Li, Jiao Xie, Donggui Hong, Chuanshen Jiang, Wen Wang
Journal: Endoscopy (2023)

Endoscopic papillectomy was first reported in Japan in 1983 [1]. It is currently recognized as an alternative to surgical resection for ampullary neoplasms, and has a higher success rate and fewer adverse events compared with open surgery [2]. At present, there are many methods of endoscopic papillectomy, but there are differences in the complete resection rate, complications, operative difficulty, and other aspects between the various methods [3] [4]. There is still a lack of consensus on the optimal method. In particular, there is controversy about whether submucosal injection is necessary [4] [5]. We propose a compromise and relatively simple innovative method, which can improve the complete resection rate of residual tissue after submucosal injection, and provide a new idea for the endoscopic resection of difficult papillary lesions.
Treating delayed perforation after esophageal endoscopic submucosal dissection using polyglycolic acid sheets and fibrin glue
Authors: Noboru Kawata, Katsuyuki Murai, Kazuya Hosotani, Hiroyuki Ono
Journal: Endoscopy (2023)

Delayed perforation after esophageal endoscopic submucosal dissection (ESD) is rare but can be a serious complication and may require surgical treatment [1]. Recently, polyglycolic acid (PGA) sheets have been used as conservative treatment for delayed perforation after ESD in the stomach [2] [3] and colon [4].
Ruptured cystic artery pseudoaneurysm after long-term transpapillary placement of a gallbladder stent for acute cholecystitis
Authors: Hirokazu Saito, Yoshitaka Kadowaki, Taishi Yamane, Ryuma Tokunaga, Yoshiaki Ikuta, Joji Urata, Shuji Tada
Journal: Endoscopy (2023)

Endoscopic transpapillary gallbladder drainage (ETGBD), including endoscopic gallbladder stenting (EGBS), has utility in the management of acute cholecystitis in patients considered to be high risk candidates for surgery [1]. A recent meta-analysis reported that the pooled rate of cholecystitis recurrence was 4.6 % following ETGBD in patients with acute cholecystitis [2]. Long-term biliary drainage via EGBS is often performed to prevent the recurrence of cholecystitis in patients with contraindications to cholecystectomy.
Developing novel antifungals: lessons from G protein-coupled receptors
Authors: Vaithish Velazhahan, Bethany L. McCann, Elaine Bignell, Christopher G. Tate
Journal: Trends in Pharmacological Sciences (2023)

Up to 1.5 million people die yearly from fungal disease, but the repertoire of antifungal drug classes is minimal and the incidence of drug resistance is rising rapidly. This dilemma was recently declared by the World Health Organization as a global health emergency, but the discovery of new antifungal drug classes remains excruciatingly slow. This process could be accelerated by focusing on novel targets, such as G protein-coupled receptor (GPCR)-like proteins, that have a high likelihood of being druggable and have well-defined biology and roles in disease. We discuss recent successes in understanding the biology of virulence and in structure determination of yeast GPCRs, and highlight new approaches that might pay significant dividends in the urgent search for novel antifungal drugs.
Underwater endoscopic mucosal resection aided by a protruding anchor created by saline injection into the distal duodenal fold
Authors: Yoshie Nomoto, Yoshimasa Miura, Hiroyuki Osawa, Chihiro Iwashita, Yuji Ino, Alan Kawarai Lefor, Hironori Yamamoto
Journal: Endoscopy (2023)

The local recurrence rate after endoscopic piecemeal resection of superficial duodenal epithelial tumors (SDETs) is high, regardless of the technique used [1], which makes it difficult to perform endoscopic salvage treatment. The ideal situation would be to achieve an en bloc resection to avoid local recurrence.
Endoscopic management of a migrated biliary stent in the pleura: a rare complication
Authors: Gaurav Patil, Ankit Dalal, Nagesh Kamat, Amol Vadgaonkar, Animesh Shah, Sehajad Vora, Amit P. Maydeo
Journal: Endoscopy (2023)

A 65-year-old woman presented with fever, cough, and right upper quadrant abdominal pain. She had undergone endoscopic retrograde cholangiopancreatography (ERCP) 3 weeks earlier for choledocholithiasis, with stent placement. There was a history of attempted stent removal, which failed, at another institute. At presentation, her laboratory parameters were normal, except for white blood cells of 22 570/µL and hemoglobin of 9 g/dL. A computed tomography scan revealed migration of the biliary stent in the pleura ([Fig. 1]).
Defining the Genetic Landscape of Idiopathic Pulmonary Fibrosis: Role of Common and Rare Variants
Authors: Benjamin J. Moss, Ivan O. Rosas
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Defining the Genetic Landscape of IPF: Role of Common and Rare Variants ." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
A simple endoscopic full-thickness plication procedure for the treatment of gastroesophageal reflux disease
Authors: Jiaoyang Lu, Rui Ji, Juan Wang, Xiuli Zuo, Yanqing Li, Xuefeng Lu
Journal: Endoscopy (2023)

Endoscopic full-thickness plication (EFTP) of the cardia or fundus has been shown to have efficacy in treating patients with gastroesophageal reflux disease (GERD) [1] [2]. However, EFTP requires proprietary equipment that may not be available in many countries. Herein, we describe a novel method of EFTP using an endoloop and metal clips, which we termed endoclip and loop cardioplication (ECLC).
Long Noncoding RNA Expression Independently Predicts Outcome in Pediatric Acute Myeloid Leukemia
Authors: Jason E. Farrar, Jenny L. Smith, Megan Othus, Benjamin J. Huang, Yi-Cheng Wang, Rhonda Ries, Tiffany Hylkema, Era L. Pogosova-Agadjanyan, Sneha Challa, Amanda Leonti, Timothy I. Shaw, Timothy J. Triche, Alan S. Gamis, Richard Aplenc, E. Anders Kolb, Xiaotu Ma, Derek L. Stirewalt, Todd A. Alonzo, Soheil Meshinchi
Journal: Journal of Clinical Oncology (2023)

Optimized strategies for risk classification are essential to tailor therapy for patients with biologically distinctive disease. Risk classification in pediatric acute myeloid leukemia (pAML) relies on detection of translocations and gene mutations. Long noncoding RNA (lncRNA) transcripts have been shown to associate with and mediate malignant phenotypes in acute myeloid leukemia (AML) but have not been comprehensively evaluated in pAML.
Multicenter Phase 2 Study of Oral azacitidine (CC-486) plus CHOP as initial treatment for peripheral T-cell lymphoma
Authors: Jia Ruan, Alison J Moskowitz, Neha Mehta-Shah, Lubomir Sokol, Zhengming Chen, Nikita Kotlov, Grigorii Nos, Maria Sorokina, Vladislav Maksimov, Andrea Sboner, Michael Sigouros, Koen van Besien, Steven M Horwitz, Sarah C. Rutherford, Erin Mulvey, María V. Revuelta, Jenny Z Xiang, Alicia Alonso, Ari M. Melnick, Olivier Elemento, Giorgio GA Inghirami, John P. Leonard, Leandro Cerchietti, Peter Martin
Journal: Blood (2023)
Modeling Heart Diseases on a Chip: Advantages and Future Opportunities
Authors: Omar Mourad, Ryan Yee, Mengyuan Li, Sara S. Nunes
Journal: Circulation Research (2023)

Heart disease is a significant burden on global health care systems and is a leading cause of death each year. To improve our understanding of heart disease, high quality disease models are needed. These will facilitate the discovery and development of new treatments for heart disease. Traditionally, researchers have relied on 2D monolayer systems or animal models of heart disease to elucidate pathophysiology and drug responses. Heart-on-a-chip (HOC) technology is an emerging field where cardiomyocytes among other cell types in the heart can be used to generate functional, beating cardiac microtissues that recapitulate many features of the human heart. HOC models are showing great promise as disease modeling platforms and are poised to serve as important tools in the drug development pipeline. By leveraging advances in human pluripotent stem cell-derived cardiomyocyte biology and microfabrication technology, diseased HOCs are highly tuneable and can be generated via different approaches such as: using cells with defined genetic backgrounds (patient-derived cells), adding small molecules, modifying the cells' environment, altering cell ratio/composition of microtissues, among others. HOCs have been used to faithfully model aspects of arrhythmia, fibrosis, infection, cardiomyopathies, and ischemia, to name a few. In this review, we highlight recent advances in disease modeling using HOC systems, describing instances where these models outperformed other models in terms of reproducing disease phenotypes and/or led to drug development.
Proliferation and Maturation: Janus and the Art of Cardiac Tissue Engineering
Authors: Bhairab N. Singh, Dogacan Yucel, Bayardo I. Garay, Elena G. Tolkacheva, Michael Kyba, Rita C.R. Perlingeiro, Jop H. van Berlo, Brenda M. Ogle
Journal: Circulation Research (2023)

During cardiac development and morphogenesis, cardiac progenitor cells differentiate into cardiomyocytes that expand in number and size to generate the fully formed heart. Much is known about the factors that regulate initial differentiation of cardiomyocytes, and there is ongoing research to identify how these fetal and immature cardiomyocytes develop into fully functioning, mature cells. Accumulating evidence indicates that maturation limits proliferation and conversely proliferation occurs rarely in cardiomyocytes of the adult myocardium. We term this oppositional interplay the proliferation-maturation dichotomy. Here we review the factors that are involved in this interplay and discuss how a better understanding of the proliferation-maturation dichotomy could advance the utility of human induced pluripotent stem cell-derived cardiomyocytes for modeling in 3-dimensional engineered cardiac tissues to obtain truly adult-level function.